Nonepileptic attacks in patients with brain tumor-related epilepsy.

Epileptic seizures are well recognized as a presenting symptom in patients with brain tumors, however much less is known about coexisting nonepileptic attack disorder (NEAD) in this population. Establishing a diagnosis of NEAD can be challenging, especially in those with concomitant epilepsy. Nonepileptic attack disorder is associated with a high rate of morbidity, often due to coexisting psychological factors which may require the input of multiple services. In an era where early aggressive management of tumors is enabling patients to live longer, the associated psychological impact of adjusting to physical disease is increasingly apparent. In this case series, we present a narrative summary of 9 patients referred to neurology with brain tumor-related epilepsy (BTRE) over a five-year period (2015-2020) who also experienced NEAD. We describe their tumor characteristics, treatment course, and factors potentially contributing to their presentation. We conducted a case note review of patients presenting to the epilepsy service with BTRE, in whom NEAD was diagnosed based on clinical features and correlation with their EEG. Patients ranged in age from 26 to 63 years. Two patients were diagnosed with grade 1, three with grade 2 and four with grade 3 tumors. Tumors localized to frontal or temporal regions in seven cases. All patients presented initially with BTRE and developed nonepileptic seizures subsequently. Four patients developed NEAD within 1 month of their tumor diagnosis. One patient developed NEAD 79 months following diagnosis. The diagnosis of NEAD was established in 8 patients by direct visualization of attacks (two during concomitant EEG recording). In the remaining patient, diagnosis was based on history (patient and witness). Six patients were diagnosed with concomitant low mood and/ or anxiety and three were commenced on antidepressant medication. At the time of last review, the predominant attacks were nonepileptic in all but one patient.

A review of the treatment of functional neurological disorder with intensive short-term dynamic psychotherapy.

The purpose of this article was to raise awareness of an under-recognized but well-supported treatment for Functional Neurological Disorders (FND) termed Intensive Short-term Dynamic Psychotherapy (ISTDP). There has been significant interest in the role of psychological mechanisms in FND onset and maintenance with specific evidence for maladaptive emotional processing. We outline how this supports the theoretical basis for ISTDP as an option in FND treatment and undertake a literature review of the current evidence base. We describe the application of ISTDP to FND illustrated through direct therapy transcripts. We conclude with reflections on the strengths and limitations of ISTDP as well as recommendations regarding future research.

Distinguishing psychogenic nonepileptic, mixed, and epileptic seizures using systemic measures and reported experiences.

OBJECTIVES: Our primary objective was to better discern features that can differentiate people with 'mixed' symptomatology from those who experience epileptic seizures (ES) or functional/psychogenic nonepileptic seizures (PNES) alone, in a population of patients referred for video-telemetry. We wished to see if we could establish the prevalence of PNES in this population of interest as well as compare both objective (e.g. videotelemetry reports and heart rate measurements) and subjective, patient-centered measures (reported symptoms and experiences). METHODS: Data were sourced from a database of all video-telemetry patients admitted to the John Radcliffe Hospital (Oxford, UK) between 1st Jan 2014 and 31st Jan 2016; video-electroencephalogram (vEEG) reports for the above patients; neurology clinic letters; multidisciplinary Team (MDT) reports; psychology assessments and patient notes for all vEEG patients referred for surgical work up. Mixed cases with a dual ES/PNES diagnosis were carefully evaluated again by the Consultant Neurologist under whose care each respective patient was, through case-by-case evaluation of EEG and telemetry reports. We compared mean heart rate during attacks captured on vEEG, number of physical symptoms reported, episode length, and postictal confusion between the three groups (ES; PNES; ES and PNES (mixed)). We evaluated the groups in terms of demographic and psychological parameters as well as prescription of anti-seizure medication. Pearson correlation significance was examined at 95% level of significance for p-values corrected for multiple comparisons. RESULTS: Overall, mixed cases reported experiencing a significantly lower number of physical symptoms compared to PNES cases (p = 0.018). The heart rate of PNES cases was significantly lower than that of mixed cases during the attacks (p = 0.003). ES patients exhibited the highest heart rate of all three groups and a greater degree of postictal confusion (adjusted p = 0.003 and p < 0.001, respectively) compared to those with PNES. There was no statistically significant difference in episode length between mixed and ES cases, while PNES patients had significantly longer episode duration (p = 0.021) compared to the mixed group. We noted that 81.6% of PNES patients were taking at least one anti-seizure medication. CONCLUSION: Patients with mixed seizures seem to be part of a spectrum between ES and PNES cases. Mixed cases are more similar to the ES group with regard to episode length and number of symptoms reported. In the PNES cohort, we found an over-reporting of ictal symptoms (e.g. palpitations, diaphoresis) disproportionate to recorded heart rate, which is lower in PNES than in epileptic attacks. This seems consistent with PNES cases experiencing a degree of impaired interoceptive processing, as part of a functional disorder spectrum. We noted that there was tendency for overmedication in the PNES group. The need for 'de-prescribing' should be addressed with measures that include better liaison with the community care team. With regard to potential autonomic dysregulation in the mixed cases, it might be interesting to see if vagus nerve stimulation could be accompanied by normalization of cardiovascular physiology parameters for people with both epileptic and psychogenic nonepileptic seizures.

Evidence of objective sleep impairment in nonepileptic attack disorder: A naturalistic prospective controlled study using actigraphy and daily sleep diaries over six nights.

Poor sleep is reported by many with nonepileptic attack disorder (NEAD) with correlations evident between self-reported sleep quality and mood and functional impairment. However, it is contended that self-reported sleep impairment in NEAD is a subjective phenomenon, which represents a general tendency to over-report symptoms or misinterpret bodily states in those with NEAD. The present study was therefore designed to investigate the extent of subjective and objective sleep impairments in those with NEAD. Over six nights we prospectively recorded comparable nightly objective (actigraphy) and subjective (consensus sleep diary) sleep parameters in a sample of 17 people with NEAD, and an age- and gender-matched normative control group (N = 20). Participants recorded daily measures of attacks, dissociation, and mood. Alongside higher subjective sleep impairment, the NEAD group had significantly worse objective sleep on several metrics compared to the normative controls, characterized by disrupted sleep (frequent awakenings and wake after sleep onset, low efficiency). Exploratory analyses using mixed effects models showed that attacks were more likely to occur on days preceded by longer, more restful sleep. This study, which had good ecological validity, evidences the presence of objective sleep impairment in NEAD, suggesting that in patient reports of problems with sleep should be given careful consideration in clinical practice.

What do patients prefer their functional seizures to be called, and what are their experiences of diagnosis? - A mixed methods investigation.

This study explored the preferred terms for functional seizures, and the experience of being diagnosed, from the patient's perspective. 39 patients in a neuropsychiatry service diagnosed with functional seizures completed an online survey to investigate preferences for, and offensiveness of, 11 common diagnostic terms used to describe functional seizures. Of these 39 patients, 13 consented to take part in a semistructured interview exploring the experience of receiving a diagnosis. Nonepileptic attack disorder (NEAD), functional seizures, functional nonepileptic attacks (FNEA), and dissociative seizures were ranked the highest preferred terms and did not significantly differ from one another. NEAD was the least offensive term, with functional seizures and FNEA following closely. Significant overlap in confidence intervals was found between the offensiveness of all terms. Terms that indicated a psychological origin were the least preferred and viewed as most offensive. Thematic analysis identified three main themes on the experience of being diagnosed: 'being heard and having a shared understanding', 'feeling alone', and 'sense of hope'. Patients favored diagnostic terms that facilitated and alleviated these themes on a personal basis; however, preferences differed across individuals. Our findings suggest that a range of terms have a similar level of preference and offense rating, with NEAD, functional seizures, and FNEA being the most favorable. Qualitative analysis indicates that a term and its accompanying explanation should facilitate shared acceptance and understanding, and several terms provide this. In combination with our previous study on healthy participants, we propose that one of the two terms researched are adopted by patients, health professionals, and the public: Functional nonepileptic attacks or Functional seizures.

Trait and state interoceptive abnormalities are associated with dissociation and seizure frequency in patients with functional seizures.

OBJECTIVE: Dissociative traits represent a disturbance in selfhood that may predispose to, and trigger, functional seizures (FSs). The predictive representation and control of the internal physiological state of the body (interoception) are proposed to underpin the integrity of the sense of self ("minimal selfhood"). Therefore, discrepancies between objective and subjective aspects of interoception may relate to symptom expression in patients with FSs. Here, we tested whether individual differences in trait measures of interoception relate to dissociative symptoms, and whether state interoceptive deficits predict FS occurrence. METHODS: Forty-one participants with FSs and 30 controls completed questionnaire ratings of dissociation, and measures of (1) interoceptive accuracy (IA)-objective performance on heartbeat detection tasks; (2) trait interoceptive sensibility-subjective sensitivity to internal sensations (using the Porges Body Perception Questionnaire); and (3) state interoceptive sensibility-subjective trial-by-trial measures of confidence in heartbeat detection. Interoceptive trait prediction error (ITPE) was calculated from the discrepancy between IA and trait sensibility, and interoceptive state prediction error (ISPE) from the discrepancy between IA and state sensibility. RESULTS: Patients with FSs had significantly lower IA and greater trait interoceptive sensibility than healthy controls. ITPE was the strongest predictor of dissociation after controlling for trait anxiety and depression in a regression model. ISPE correlated significantly with FS frequency after controlling for state anxiety. SIGNIFICANCE: Patients with FSs have disturbances in interoceptive processing that predict both dissociative traits reflecting the disrupted integrity of self-representation, and the expression of FSs. These findings provide insight into the pathophysiology of functional neurological disorder, and could lead to novel diagnostic and therapeutic approaches.

Nonepileptic attack disorder and functional movement disorder: A clinical continuum?

Nonepileptic attack disorder (NEAD) and functional movement disorder (FMD) are functional neurological disorders commonly seen in neuropsychiatry services. Although their initial referral pathways involve epileptologists (NEAD) and specialists in movement disorders (FMD), these conditions are currently classified as two possible manifestations of a single underlying conversion disorder. We set out to compare the characteristics of patients with NEAD and patients with FMD in order to quantify the degree of overlap between these patient groups. We retrospectively reviewed comprehensive clinical data from 146 consecutive patients with functional neurological disorders (NEAD: n = 117; FMD: n = 29) attending a specialist Neuropsychiatry Clinic run by a single Consultant in Behavioral Neurology. The two clinical groups were directly compared with regard to demographic and clinical characteristics, as well as somatic and psychiatric presentations. The results showed that in most features, there were no significant differences between patients with NEAD and patients with FMD. However, patients with NEAD reported an earlier age at onset (p = 0.033) and a higher proportion of acute onset (p = 0.037), alterations of consciousness (p = 0.001), and headache (p = 0.042), whereas patients with FMD reported a higher prevalence of childhood abuse (p = 0.008), as well as mobility problems (p = 0.007) and comorbid functional symptoms (dysarthria, p = 0.004; dizziness, p = 0.035; weakness, p = 0.049). Despite different phenotypic presentations, NEAD and FMD might represent a clinical continuum, with relevant implications in terms of both diagnostic strategies and treatment approaches.

Levels of diagnostic certainty for nonepileptic attack disorder in the neuropsychiatry setting.

Nonepileptic attack disorder (NEAD) is a medical condition commonly seen in neuropsychiatry services, often as a differential diagnosis of other neuropsychiatric conditions. Recommendations by the International League Against Epilepsy (ILAE) Nonepileptic Seizures Task Force propose a four-level hierarchical approach to the diagnosis of NEAD, based on history, witnessed event, and electroencephalographic (EEG) investigation. We set out to provide the first description of the diagnostic levels of patients with NEAD at a specialist neuropsychiatry clinic. Comprehensive clinical data from 148 consecutive patients with NEAD attending the specialist Neuropsychiatry Clinic run by a single Consultant in Behavioral Neurology were retrospectively reviewed. Patients with NEAD were primarily referred to neuropsychiatry by Consultant Neurologists (n = 94; 63.5%). The majority of patients were female (n = 108; 73.0%), with a disease duration of 7.9 years (standard deviation: 10.4). Anxiety was the most common comorbidity (n = 43; 26.7%). Categorization of patients according to the ILAE Nonepileptic Seizures Task Force criteria was mainly based on clinical features and EEG findings, as only 7 (4.7%) patients had attacks witnessed by a specialist. The largest diagnostic categories were 'possible' (n = 54; 36.5%) and 'clinically established' (n = 40; 27.0%), followed by 'documented' (n = 12; 8.1%) and 'probable' (n = 5; 3.4%). In 125 patients (84.4%), EEGs were performed. Selective serotonin reuptake inhibitors were the most frequently prescribed psychotropic medications (n = 48; 32.4%); 89 patients (60.1%) received behavioral therapy. There were no differences in pharmacological or behavioral management strategies across the patients categorized under different diagnostic levels. Patients with NEAD seen within neuropsychiatry settings are mainly assigned 'possible' and 'clinically established' levels of diagnostic certainty. Difficulty in capturing typical clinical events witnessed by an experienced clinician while on video-EEG can limit the clinical application of the 'documented' diagnostic level. If appropriate, active interventions can be implemented irrespective of diagnostic levels to minimize delays in the neuropsychiatric care pathways.

Psychological inflexibility and somatization in nonepileptic attack disorder.

BACKGROUND: There is no clear understanding of what causes and maintains nonepileptic attack (NEA) disorder (NEAD), or which psychological therapies may be helpful. The relationships between variables of psychological inflexibility: experiential avoidance (EA), cognitive fusion (CF), mindfulness, and key outcome variables in NEAD: somatization, impact upon life, and NEA frequency were investigated. METHOD: Two hundred eighty-five individuals with NEAD completed validated measures online. Linear regression was used to explore which variables predicted somatization and impact upon life. Ordinal regression was used to explore variables of interest in regard to NEA frequency. RESULTS: Mindfulness, EA, CF, somatization, and impact upon life were all significantly correlated. Mindfulness uniquely predicted somatization when considered in a model with EA and CF. Higher levels of somatization increased the odds of experiencing more NEAs. Individuals who perceived NEAD as having a more significant impact upon their lives had more NEAs, more somatic complaints, and more EA. CONCLUSIONS: Higher levels of CF and EA appear to be related to lower levels of mindfulness. Lower levels of mindfulness predicted greater levels of somatization, and somatization predicted NEA frequency. Interventions that tackle avoidance and increase mindfulness, such as, acceptance and commitment therapy, may be beneficial for individuals with NEAD. Future directions for research are suggested as the results indicate more research is needed.

An investigation into the preferred terminology for functional seizures.

There is considerable debate in the literature regarding what to call functional seizures, with terms such as pseudoseizures, nonepileptic attack disorder (NEAD), and dissociative seizures being used. Provision of an accurate diagnosis and coherent explanation is a vital first step in the management of functional seizures and can result in cessation or reduced frequency for some individuals. This study investigated preferences for and offensiveness of terms used to describe functional seizures, and expectations for recovery with psychological treatment. A sample of 87 healthy adults completed an online survey, in which eight different diagnostic terms were ranked in order of preference (1 - most preferred, 8 - least preferred): functional nonepileptic attacks (FNEA), dissociative seizures, functional seizures, psychogenic seizures, NEAD, pseudoseizures, conversion disorder, and hysteria. Replicating Stone and colleagues protocol, each term was investigated for five connotations. Offense scores were calculated from the number of participants who selected 'yes' to at least one of the negative connotations ('Putting it on', 'Mad', and 'Imagining Symptoms'). Expectations about the possibility of recovering through medical or psychological treatment were also recorded. Functional nonepileptic attack was ranked the highest preferred term with dissociative seizures and functional seizures closely following. Nonepileptic attack disorder was the least offensive term, with FNEA and functional seizures joint second. Unsurprisingly, the three least preferred terms were also the most offensive: pseudoseizures, conversion disorder, and hysteria. Expectations of nonrecovery from psychological treatment were lowest for terms implicating a psychological cause: pseudoseizures, dissociative seizures, psychogenic seizures, and hysteria. The results suggest that either the terms FNEA or functional seizures should be adopted by healthcare professionals and patients, as they are the most preferred, least offensive, and expectations for nonrecovery with psychological treatment were moderate compared with the other terms. Limitations and areas for future research are discussed.